The release of free fatty acids from cellular membranes has been implicated in attenuating the blood-brain barrier (BBB) permeability under pathological conditions. This continuous study is concerned with elucidation of mechanisms involved with an arachidonate inducible increase permeability of cerebromicrovascular endothelium using a model system in vitro consisting of cultured endothelial cells derived from cerebral microvessels. The investigations focused on the relationship between the "fluidity" of endothelial membrane and permeability of cells exposed to AA alone or to AA and H202. These studies demonstrate that AA modification of endothelial membrane "fluidity" does not affect the permeability of those cells. Conversely, an absence of increased membrane "fluidity" and an augmented TBA permeability of endothelium is associated with AA and H202 treatment. These findings support the contention that the release of arachidonate from cellular membrane under pathological conditions may alter BBB function by changing either the membrane "fluidity" or cellular permeability.